Despite its prominent position in bedside care, there is little evidence to judge the benefits or associated risks of nurse-administered tooth brushing for mechanically ventilated adults, and the optimal frequency of tooth brushing in the critically il has never been experimentally determined. This project will complete the examination of oral care interventions in mechanically ventilated adults with a randomized clinical trial of tooth brushing frequency (once, twice, or three times daily) focused on conclusively defining the benefit and risk of varied frequencies, and identification of moderating patient-level factors for risk and benefit. The project's overall goal is to determine optimal tooth brushing frequency for mechanically ventilated adults. Optimal tooth brushing frequency is important for control of dental plaque and reduction of oral inflammation; it is likely to improve patient comfort, improve efficiency of nursing care, and may reduce systemic sequellae related to oral inflammation. The primary aims of the proposed project are: 1) Evaluate the clinical equivalence (non- inferiority) o three tooth brushing frequencies on oral health (dental plaque and mucosal inflammation) in critically ill adults receiving mechanical ventilation; and 2) Quantify and compare the safety of three tooth brushing frequencies on serious adverse outcomes, including ventilator associated complications and clinically relevant HAIs. A secondary aim is to investigate patient factors that influence tooth brushing frequency benefit and risk in critically ill adults. These objectives willbe accomplished using a prospective, randomized, experimental design. Subjects (n=345) will be randomly assigned within 24 hours of intubation to one of three intervention groups which differ in frequency of tooth brushing delivered by study personnel (once, twice, or three times daily). Dental plaque (UM-OHI score, with observations documented and augmented by use of a digital intraoral camera), mucosal inflammation (gingival crevicular fluid IL-1?), and HAIs will be assessed daily during the intervention period. The data analysis will focus on providing definitive clinical practice guidance through joint evaluation of non-inferiority (comparison of dental plaque between groups by analysis of covariance) and quantification of number needed to harm. Repeated measures linear mixed models (treating dental plaque and mucosal inflammation as separate outcome variables) will provide insight as to specific patient-level factors that may modify the clinical effectiveness and safety profile associated with frequency of tooth brushing. Information about efficacy and safety of each frequency of tooth brushing will provide a clear recommendation for optimal tooth brushing frequency with direct translation to clinical practice.